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Building Knowledgebase for Neuroscience: Eric Prud’hommeaux, W3C BioRDF

This task aims to build a knowledge base for neuroscience using RDF/OWL to better understand the value of the Semantic Web in the life sciences. It involves exploring the effectiveness of current tools, documenting findings, and building a demo.

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Building Knowledgebase for Neuroscience: Eric Prud’hommeaux, W3C BioRDF

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  1. BioRDF Task: Building a Knowledgebase for Neuroscience • Eric Prud’hommeaux, W3C

  2. BioRDF Introduction • BioRDF participants • The task is lead by Kei Cheung (Yale) • Has approximately 20 participants • BioRDF activities include: • Explore the effectiveness of current tools for making data available as RDF/OWL • Build a life sciences demo that spans from bench to bedside using RDF/OWL to help scientist better understand the value of the Semantic Web • Document our finding to help accelerate the adoption of the Semantic Web by others • BioRDF Publications • A Prototype Knowledge Base for the Life Sciences - http://www.w3.org/TR/hcls-kb/ • Experience with the Conversion of SenseLab Databases to RDF/OWL – http://www.w3.org/TR/hcls-senselab/ • More Information on the group is available at • http://esw.w3.org/topic/HCLSIG_BioRDF_Subgroup

  3. Answering Questions • Goals: Get answers to questions posed to a body of collective knowledge in an effective way • Knowledge used: Publicly available databases, and text mining • Strategy: Integrate knowledge using careful modeling, exploiting Semantic Web standards and technologies

  4. Looking for Alzheimer Disease Targets • Signal transduction pathways are considered to be rich in “druggable” targets • CA1 Pyramidal Neurons are known to be particularly damaged in Alzheimer’s disease • Casting a wide net, can we find candidate genes known to be involved in signal transduction and active in Pyramidal Neurons?

  5. Answering Questions with Google

  6. Answering Questions with PubMed

  7. Answering Questions across Data Sets

  8. PDSPki Reactome Gene Ontology NeuronDB BAMS Entrez Gene Antibodies Allen Brain Atlas BrainPharm Literature SWAN Homologene PubChem AlzGene Mammalian Phenotype MESH Integrating Heterogeneous Data Sets

  9. Integrating Heterogeneous Data Sets

  10. Integrating Heterogeneous Data Sets PDSPki NeuronDB Reactome Gene Ontology BAMS Allen Brain Atlas BrainPharm Antibodies Entrez Gene MESH Literature PubChem Mammalian Phenotype SWAN AlzGene Homologene

  11. SPARQL Query Spanning Data Sources

  12. Results: Genes, Processes • DRD1, 1812 adenylate cyclase activation • ADRB2, 154 adenylate cyclase activation • ADRB2, 154 arrestin mediated desensitization of G-protein coupled receptor protein signaling pathway • DRD1IP, 50632 dopamine receptor signaling pathway • DRD1, 1812 dopamine receptor, adenylate cyclase activating pathway • DRD2, 1813 dopamine receptor, adenylate cyclase inhibiting pathway • GRM7, 2917 G-protein coupled receptor protein signaling pathway • GNG3, 2785 G-protein coupled receptor protein signaling pathway • GNG12, 55970 G-protein coupled receptor protein signaling pathway • DRD2, 1813 G-protein coupled receptor protein signaling pathway • ADRB2, 154 G-protein coupled receptor protein signaling pathway • CALM3, 808 G-protein coupled receptor protein signaling pathway • HTR2A, 3356 G-protein coupled receptor protein signaling pathway • DRD1, 1812 G-protein signaling, coupled to cyclic nucleotide second messenger • SSTR5, 6755 G-protein signaling, coupled to cyclic nucleotide second messenger • MTNR1A, 4543 G-protein signaling, coupled to cyclic nucleotide second messenger • CNR2, 1269 G-protein signaling, coupled to cyclic nucleotide second messenger • HTR6, 3362 G-protein signaling, coupled to cyclic nucleotide second messenger • GRIK2, 2898 glutamate signaling pathway • GRIN1, 2902 glutamate signaling pathway • GRIN2A, 2903 glutamate signaling pathway • GRIN2B, 2904 glutamate signaling pathway • ADAM10, 102 integrin-mediated signaling pathway • GRM7, 2917 negative regulation of adenylate cyclase activity • LRP1, 4035 negative regulation of Wnt receptor signaling pathway • ADAM10, 102 Notch receptor processing • ASCL1, 429 Notch signaling pathway • HTR2A, 3356 serotonin receptor signaling pathway • ADRB2, 154 transmembrane receptor protein tyrosine kinase activation (dimerization) • PTPRG, 5793 ransmembrane receptor protein tyrosine kinase signaling pathway • EPHA4, 2043 transmembrane receptor protein tyrosine kinase signaling pathway • NRTN, 4902 transmembrane receptor protein tyrosine kinase signaling pathway • CTNND1, 1500 Wnt receptor signaling pathway Many of the genes are related to AD through gamma secretase (presenilin) activity

  13. Another View of the Query http://hcls1.csail.mit.edu:8890/sparql/?query=prefix%20go%3A%20%3Chttp%3A%2F%2Fpurl.org%2Fobo%2Fowl%2FGO%23%3E%0Aprefix%20rdfs%3A%20%3Chttp%3A%2F%2Fwww.w3.org%2F2000%2F01%2Frdf-schema%23%3E%0Aprefix%20owl%3A%20%3Chttp%3A%2F%2Fwww.w3.org%2F2002%2F07%2Fowl%23%3E%0Aprefix%20mesh%3A%20%3Chttp%3A%2F%2Fpurl.org%2Fcommons%2Frecord%2Fmesh%2F%3E%0Aprefix%20sc%3A%20%3Chttp%3A%2F%2Fpurl.org%2Fscience%2Fowl%2Fsciencecommons%2F%3E%0Aprefix%20ro%3A%20%3Chttp%3A%2F%2Fwww.obofoundry.org%2Fro%2Fro.owl%23%3E%0A%0Aselect%20%3Fgenename%20%3Fprocessname%0Awhere%0A%7B%20%20graph%20%3Chttp%3A%2F%2Fpurl.org%2Fcommons%2Fhcls%2Fpubmesh%3E%0A%20%20%20%20%20%7B%20%3Fpaper%20%3Fp%20mesh%3AD017966%20.%0A%20%20%20%20%20%20%20%3Farticle%20sc%3Aidentified_by_pmid%20%3Fpaper.%0A%20%20%20%20%20%20%20%3Fgene%20sc%3Adescribes_gene_or_gene_product_mentioned_by%20%3Farticle.%0A%20%20%20%20%20%7D%0A%20%20%20graph%20%3Chttp%3A%2F%2Fpurl.org%2Fcommons%2Fhcls%2Fgoa%3E%0A%20%20%20%20%20%7B%20%3Fprotein%20rdfs%3AsubClassOf%20%3Fres.%0A%20%20%20%20%20%20%20%3Fres%20owl%3AonProperty%20ro%3Ahas_function.%0A%20%20%20%20%20%20%20%3Fres%20owl%3AsomeValuesFrom%20%3Fres2.%0A%20%20%20%20%20%20%20%3Fres2%20owl%3AonProperty%20ro%3Arealized_as.%0A%20%20%20%20%20%20%20%3Fres2%20owl%3AsomeValuesFrom%20%3Fprocess.%0A%20%20%20graph%20%3Chttp%3A%2F%2Fpurl.org%2Fcommons%2Fhcls%2F20070416%2Fclassrelations%3E%0A%20%20%20%20%20%7B%7B%3Fprocess%20%3Chttp%3A%2F%2Fpurl.org%2Fobo%2Fowl%2Fobo%23part_of%3E%20go%3AGO_0007166%7D%0A%20%20%20%20%20%20%20union%0A%20%20%20%20%20%20%7B%3Fprocess%20rdfs%3AsubClassOf%20go%3AGO_0007166%20%7D%7D%0A%20%20%20%20%20%20%20%3Fprotein%20rdfs%3AsubClassOf%20%3Fparent.%0A%20%20%20%20%20%20%20%3Fparent%20owl%3AequivalentClass%20%3Fres3.%0A%20%20%20%20%20%20%20%3Fres3%20owl%3AhasValue%20%3Fgene.%0A%20%20%20%20%20%20%7D%0A%20%20%20graph%20%3Chttp%3A%2F%2Fpurl.org%2Fcommons%2Fhcls%2Fgene%3E%0A%20%20%20%20%20%7B%20%3Fgene%20rdfs%3Alabel%20%3Fgenename%20%7D%0A%20%20%20graph%20%3Chttp%3A%2F%2Fpurl.org%2Fcommons%2Fhcls%2F20070416%3E%0A%20%20%20%20%20%7B%20%3Fprocess%20rdfs%3Alabel%20%3Fprocessname%7D%0A%7D&format=&maxrows=50

  14. Discoverable, Queryable and Accessible on the Web Allen Brain Institute Servers http://hcls1.csail.mit.edu/map/#Kcnip3@2850,Kcnd1@2800 Javascript http://www.brainmap.org://….0205032816_B.aff/TileGroup3/1-0-1.jpg SPARQLAJAX URL Query GoogleMapsAPI Neurocommons Servers

  15. Use Exhibit to Visualize Results

  16. Technology So far about 350M triples (~20Gb on disk) Openlink Virtuoso - open source triple store Commodity Hardware: 2x2core duo/2 disks/8G Ram

  17. Going Forwards Incorporate additional data sources into the HCLS KB Make the interface easier for scientists to use Focus on processes for updating the data sources Find additional places to host the HCLS KB

  18. Conclusions • The Semantic Web offers a flexible approach to data integration • BioRDF has integrated over a dozen neuroscience related resources to simplify answering scientific questions • The HCLS KB is accessible on the Web today • Please let us know if you are interested in participating in the BioRDF task

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